Pathway of free fatty acid oxidation in human subjects. Implications for tracer studies

To determine the pathway of plasma FFA oxidation and the site(s) of label fixation observed during infusion of FFA tracers, [1-l'3C]palmitate and [1- 4Clacetate were infused intravenously for 3 h in five volunteers. Breath 1'3CO2 enrich-ment and "CO2 specific activity were followed for 6 h to determine the labeled CO2 decay rates. Acetate enters di-rectly into the TCA cycle; hence, if palmitate transits a large lipid pool before oxidation, '3CO2 enrichment (from palmitate) should decay slower than 1'CO2 specific activity (from acetate). Breath "3CO2 enrichment and "CO2 specific activity decayed at a similar rate after stopping the tracer infusions (half-lives of 13CO2 and "CO2 decay: mean [±SE] 106.6±8.9 min, and 96.9±6.0 min, respectively, P = NS), which suggests that palmitate enters the TCA cycle directly and that label fixation occurs after citrate synthesis. Signifi-cant label fixation was shown in plasma glutamate/gluta-mine and lactate/pyruvate during infusion of either [1,2-13C]acetate or [U-13C]palmitate, suggesting that TCA cycle exchange reactions are at least partly responsible for label fixation. This was consistent with our finding that the half-lives of 13CO2 enrichment and 1"CO2 specific activity de-creased significantly during exercise to 14.4±3 min and 16.8±1 min, respectively, since exercise significantly in-creases the rate of the TCA cycle in relation to that of the TCA cycle exchange reactions. We conclude that plasma FFA entering cells destined to be oxidized are directly oxi-dized and that tracer estimates of plasma FFA oxidation will underestimate the true value unless account is taken of the extent of label fixation. (J. Clin. Invest. 1995. 95:278-284.) Key words: exercise * isotopes * tricarboxylic acid cycle * triacylglycerols- acetat